Two methodologies are proposed to study the contribution of somatic diversification to the repertoire of specificities expressed by an individual. They are a) the analysis of antigen specific responsiveness in genetically dissected animals and b) the development of cell lines characteristically responsive to antigen. a) Alpha(1,3) dextran induces in the prototype mouse (BALB/c) a restricted antibody whose V-regions are coded by a single germ-line vlambda-gene and one of two closely related germ-line vHlambda alpha(1,3)-genes. Mice which fail to express either of these genes are unresponsive to alpha(1,3) dextran unless a strong immunogenic pressure is put on them in which case they produce a kappa-class anti-alpha(1,3) dextran response. The proposal is to study the structure of the antibody induced in strains with various kappa- and H-chain loci but lacking responsiveness of the lambda-mode. Such strains reveal a behavior indicative of somatic variation. b) By purification for antigen-sensitive cells with known specificities and accessory cells with known function we hope to increase our chances of obtaining cloned lines of known function by transforming them with oncogenic viruses and carcinogens. These cells will be screened for function in replacing the various elements in an in vitro immune response. With such lines studies will be carried out on allelic exclusion, linkage relationships of structural immunoglobulin genes to histocompatibility markers, mechanism of cell-cell interactions and somatic and germ-line diversification.